Higher mammals, such as humans, have markedly larger brains than other
mammals. Scientists from the Max Planck Institute of Molecular Cell
Biology and Genetics in Dresden recently discovered a new mechanism
governing brain stem cell proliferation. It serves to boost the
production of neurons during development, thus causing the enlargement
of the cerebral cortex -- the part of the brain that enables us humans
to speak, think and dream.
The surprising discovery
made by the Dresden-based researchers: two components in the stem cell
environment -- the extracellular matrix and thyroid hormones -- work
together with a protein molecule found on the stem cell surface, a
so-called integrin. This likely explains why iodine deficiency in
pregnant women has disastrous consequences for the unborn child,
affecting its brain development adversely -- without iodine, no thyroid
hormones are produced. "Our study highlights this relationship and
provides a potential explanation for the condition neurologists refer to
as cretinism," says Wieland Huttner, Director at the Max Planck
Institute in Dresden. This neurological disorder severely impairs the
mental abilities of a person.
In the course of evolution, certain
mammals, notably humans, have developed larger brains than others, and
therefore more advanced cognitive abilities. Mice, for example, have
brains that are around a thousand times smaller than the human one. In
their study, which was conducted in cooperation with the Fritz Lipmann
Institute in Jena, the researchers in Dresden wanted to identify factors
that determine brain development, and understand how larger brains have
evolved.
A cozy bed for brain stem cells
Brain
neurons are generated from stem cells called basal progenitors that are
able to proliferate in humans, but not in mice. In humans, basal
progenitors are surrounded by a special environment, a so-called
extracellular matrix (ECM), which is produced by the progenitors
themselves. Like a cosy bed, it accommodates the proliferating cells.
Mice lack such ECM, which means that they generate fewer neurons and
have a smaller brain.
The scientists therefore conducted tests to
see whether in mice, basal progenitors start to proliferate if a
comparable cell environment is simulated. The result: "We simulated an
extracellular matrix for the brain stem cells using a stimulating
antibody. This antibody activates an integrin on the cell surface of
basal progenitors and thus stimulates their proliferation," explains
Denise Stenzel, who headed the experiments.
Because a requirement
of thyroid hormones for proper brain development was previously known,
the researchers blocked the production of these hormones in pregnant
rats to see if their absence would inhibit basal progenitor
proliferation in the embryos. Indeed, fewer progenitors and,
consequently, neurons were produced, likely explaining the abnormal
brain development in the absence of thyroid hormones. When the action of
these hormones on the integrin was blocked, the ECM-simulating antibody
alone was no longer able to induce basal progenitor proliferation.
A
combination of ECM and thyroid hormones thus appears necessary for
basal progenitors to proliferate and produce enough neurons for brain
development. Human brain stem cells produce the suitable environment
naturally. "That is probably how, in the course of evolution, we humans
developed larger brains," says Wieland Huttner, summing up the study.
The research produced another important finding: "We were able to
explain the role of iodine in embryonic brain development at the
cellular level," says Denise Stenzel. Iodine is essential for the
production of thyroid hormones, and an iodine deficiency in pregnant
women is known to have adverse effects on the brain development of the
unborn child.
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